Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study
| Autor: | Eduardo Díaz-Rubio, Auxiliadora Gómez-España, Bartomeu Massutí, Javier Sastre, Margarita Reboredo, José Luis Manzano, Fernando Rivera, M José Safont, Clara Montagut, Encarnación González, Manuel Benavides, Eugenio Marcuello, Andrés Cervantes, Purificación Martínez de Prado, Carlos Fernández-Martos, Antonio Arrivi, Inmaculada Bando, Enrique Aranda, Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) |
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| Přispěvatelé: | The Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), [Díaz-Rubio,E, Sastre,J, Bando,I] Department of Medical Oncology, Hospital Clínico San Carlos (HCSC), Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0021), Facultad de Medicina, Universidad Complutense, Instituto de Investigación Sanitaria del HCSC (IdISSC), Madrid, Spain. [Gómez-España,A, Aranda,E] Department of Medical Oncology, Hospital Reina Sofía, Córdoba, Spain. [Massutí,B] Department of Medical Oncology, Hospital General, Alicante, Spain. [Reboredo,M] Department of Medical Oncology, Complejo Hospitalario Universitario La Coruña, La Coruña, Spain. [Manzano, JL] Department of Medical Oncology, Instituto Catalán de Oncología, Hospital Germans Trias I Pujol, Badalona, Spain. [Rivera,F] Department of Medical Oncology, Hospital Marqués de Valdecilla, Santander, Spain. [Safont,MJ] Department of Medical Oncology, Hospital General de Valencia, Valencia, Spain. [Montagut,C] Department of Medical Oncology, Hospital del Mar, Barcelona, Spain. [González,E] Department of Medical Oncology, Hospital Virgen de las Nieves, Granada, Spain. [Benavides,M] Department of Medical Oncology, Hospital Universitario Carlos Haya, Málaga, Spain. [Marcuello,E] Department of Medical Oncology, Hospital Santa Creu i Sant Pau, Barcelona, Spain. [Cervantes,A] Department of Medical Oncology, Institute of Health Research INCLIVA. University of Valencia, Valencia, Spain. [Martínez de Prado, P] Department of Medical Oncology, Hospital de Basurto, Vizcaya, Spain. [Fernández-Martos, C] Department of Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain. [Arrivi,A] Department of Medical Oncology, Fundación Hospital Son Llatzer, Palma de Mallorca, Spain., This work was supported by Roche |
| Rok vydání: | 2012 |
| Předmět: |
Male
Oncology Organoplatinum Compounds endocrine system diseases Epidemiology Colorectal cancer Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] Deoxycytidine Metastasis Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Antineoplastic Combined Chemotherapy Protocols Pathology Medicine Neoplasm Metastasis genes lcsh:Science mediana edad Analytical Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [Medical Subject Headings] Aged 80 and over anciano Chemicals and Drugs::Organic Chemicals::Organometallic Compounds::Organoplatinum Compounds [Medical Subject Headings] Cancer Risk Factors Clinical Pharmacology protocolos de quimioterapia antineoplásica combinada Colon Adenocarcinoma Pronóstico Combination chemotherapy adulto Prognosis Bevacizumab Oxaliplatin pronóstico Oncology Agents medicine.medical_specialty Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings] Fluorouracilo Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Pyrimidines::Pyrimidine Nucleosides::Cytidine::Deoxycytidine [Medical Subject Headings] Check Tags::Male [Medical Subject Headings] Molecular Genetics Capecitabine Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies Monoclonal::Antibodies Monoclonal Humanized [Medical Subject Headings] Gastrointestinal Tumors Genetics Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] Humans Clinical Trials Biology neoplasms Aged lcsh:R Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings] Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes Neoplasm::Oncogenes::Proto-Oncogenes::Genes ras [Medical Subject Headings] medicine.disease digestive system diseases Check Tags::Female [Medical Subject Headings] Pharmacogenetics Mutation lcsh:Q fluorouracilo Multivariate analysis Desoxicitidina humanos Cancer Treatment Named Groups::Persons::Age Groups::Adult::Aged::Aged 80 and over [Medical Subject Headings] lcsh:Medicine medicine.disease_cause Neoplasias colorrectales Surgical oncology Basic Cancer Research Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil [Medical Subject Headings] Clinical Trials (Cancer Treatment) metástasis neoplásica Metástasis neoplásica Multidisciplinary Middle Aged Genetic Epidemiology Protocolos de quimioterapia antineoplásica combinada Female Antiangiogenesis Therapy Fluorouracil KRAS Colorectal Neoplasms Research Article medicine.drug Adult Drugs and Devices Clinical Pathology neoplasias colorrectales Clinical Research Design Genetic Causes of Cancer Antibodies Monoclonal Humanized Antibodies Rectal Cancer Antibody Therapy Diagnostic Medicine Internal medicine Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings] Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings] mutación Clinical Genetics Mutación business.industry Pharmacoepidemiology Cancers and Neoplasms Human Genetics Chemotherapy and Drug Treatment desoxicitidina Genes ras anticuerpos Genetics of Disease business compuestos organoplatino |
| Zdroj: | PLoS ONE, Vol 7, Iss 10, p e47345 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0047345 |
| Popis: | Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI: 1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18-2.64). Conclusions/Significance: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses. This work was supported by Roche (www.roche.es) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Databáze: | OpenAIRE |
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